Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure.

Conclusions: Our results indicate that a moderate increase in PDE4B is cardioprotective and suggest that cardiac gene therapy with PDE4B might constitute a new promising approach to treat HF. PMID: 32264695 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research

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Discussion of the Evolutionary Genetics of Aging Thymic Involution Contributes to Immunosenescence and Inflammaging The Potential for Exosome Therapies to Treat Sarcopenia Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice The Aging Retina, a Mirror of the Aging Brain Evidence for Loss of Capillary Density to be Important in Heart Disease Aspects of Immune System Aging Proceed More Rapidly in Men Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation Transplantation of Senescent Cells is an ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Telomerase gene therapy is considered in some quarters to be a viable treatment for aging. Telomeres are the caps of repeated DNA sequences at the ends of chromosomes. They are an important part of the mechanism limiting the number of times that somatic cells in the body can divide, the Hayflick limit. A little telomere length is lost with each cell division, and short telomeres trigger cellular senescence or programmed cell death, halting replication. Stem cell populations use telomerase to lengthen their telomeres and thus self-renew to provide a continual supply of new somatic daughter cells with long telomeres to repla...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
In conclusion, high-dose NR induces the onset of WAT dysfunction, which may in part explain the deterioration of metabolic health. Towards a Rigorous Definition of Cellular Senescence https://www.fightaging.org/archives/2019/11/towards-a-rigorous-definition-of-cellular-senescence/ The accumulation of lingering senescent cells is a significant cause of aging, disrupting tissue function and generating chronic inflammation throughout the body. Even while the first senolytic drugs capable of selectively destroying these cells already exist, and while a number of biotech companies are working on the productio...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we developed gene therapies based on 3 longevity associated genes: fibroblast growth factor 21 (FGF21), αKlotho, soluble form of mouse transforming growth factor-β receptor 2 (sTGFβR2). The gene therapies were delivered using adeno-associated viruses, and we explored their ability to mitigate 4 age-related diseases: obesity, type II diabetes, heart failure, and renal failure. Individually and combinatorially, we applied these therapies to disease-specific mouse models and found that this set of diverse pathologies could be effectively treated and in some cases, even reversed with a sin...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Adeno-associated virus (AAV) vectors have become one of the most widely used systems for gene delivery. These vectors have been tested in a diverse range of pre-clinical models, ranging from liver disease to heart failure, with highly promising results. In fact, there were over 100 abstracts presented at the American Society of Gene and Cell Therapy (ASGCT) 21st Annual Meeting in Chicago in 2018 that described the use of AAV vectors in pre-clinical or clinical studies. A quick review of selected categories related to gene delivery revealed that AAV comprised nearly half of the abstracts describing the use of viral or non-v...
Source: Heart, Lung and Circulation - Category: Cardiology Authors: Tags: Editorial Source Type: research
ConclusionHuman plasma and cardiac IGFBP2 are decreased in MetS patients. In mice, restoration of cardiac IGFBP2 expression level prevents MetS associated left ventricular dysfunction and hypertrophy. These clinical and animal data suggest that IGFBP2 is a new cardiac marker and therapeutic target in MetS to prevent heart remodeling consistent with heart failure.
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
Conclusions: Inhibition of CIB1 by a shRNA-mediated gene-therapy potently inhibits pathological cardiac hypertrophy and fibrosis during pressure overload. While cardiac function is initially improved by shCIB1, this cannot be kept up during persisting overload. PMID: 29931050 [PubMed - as supplied by publisher]
Source: Hamostaseologie - Category: Hematology Authors: Tags: Cardiovasc Res Source Type: research
Abstract Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis ...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
This study was performed to evaluated the safety and efficacy of Ad-HGF by percutaneous endocardial injection for treating post-infarct heart failure. METHODS: A total of 30 patients (15 in the experimental group and 15 in the control group) with post-infarct heart failure who were not indicated to revascularization and had received the optimal standardized medication therapy were included in the study. Percutaneous endocardial Ad-HGF gene transfer was injected with a catheter-based intramyocardial delivery system in the experimental group. Safety parameters were measured and compared between baseline and follow-ups i...
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research
Despite advances in treatment over the past decade, heart failure remains a significant public health burden and a leading cause of death in the developed world. Gene therapy provides a promising approach for preventing and reversing cardiac abnormalities, however, clinical application has shown limited success to date. A substantial effort is being invested into the development of recombinant adeno-associated viruses (AAVs) for cardiac gene therapy as AAV gene therapy offers a high safety profile and provides sustained and efficient transgene expression following a once-off administration.
Source: Heart, Lung and Circulation - Category: Cardiology Authors: Tags: Review Source Type: research
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